ATP-binding cassette transporter A1 (ABCA1) deficiency does not attenuate the brain-to-blood efflux transport of human amyloid-beta peptide (1-40) at the blood-brain barrier.

Abstract

ATP-binding cassette transporter A1 (ABCA1) mediates apolipoprotein-dependent cholesterol release from cellular membranes. Recent studies using ABCA1 knockout mice have demonstrated that ABCA1 affects amyloid-beta peptide (A beta) levels in the brain and the production of senile plaque. Cerebral A beta(1-40) was eliminated from the brain to the circulating blood via the blood-brain barrier (BBB), which expresses ABCA1. Therefore, in the present study, we examined whether ABCA1 affects the brain-to-blood efflux transport of human A beta(1-40)(hA beta(1-40)) at the BBB. The apparent uptake of [125I]hA beta(1-40) into ABCA1-expressing HEK293 cells was not significantly different from that into parental HEK293 cells. In addition, the apparent uptake was not significantly affected even in the presence of apolipoprotein A-I as a cholesterol release acceptor. Moreover, [125I]hA beta(1-40) elimination from mouse brain across the BBB was not significantly different between ABCA1-deficient and wild-type mice 60 min after its administration into the cerebrum. These results suggest that ABCA1 does not directly transport hA beta(1-40) and a deficiency of ABCA1 does not attenuate the brain-to-blood efflux transport of hA beta(1-40) across the BBB.

• Authors: Shin-ichi Akanuma, Sumio Ohtsuki, Youko Doi, Masanori Tachikawa, Shingo Ito, Satoko Hori, Tomoko Asashima, Tadafumi Hashimoto, Kaoru Yamada, Kazumitsu Ueda, Takeshi Iwatsubo, Tetsuya Terasaki
• Journal: Neurochemistry international (Neurochem Int) Vol. 52 Issue 6 Pg. 956-61 (May 2008) ISSN: 0197-0186 [Print] England
• PMID: 18201804 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCA1 protein, human
• ATP Binding Cassette Transporter 1
• ATP-Binding Cassette Transporters
• Amyloid beta-Peptides
• Apolipoprotein A-I
• Peptide Fragments
• amyloid beta-protein (1-40)

Topics

• ATP Binding Cassette Transporter 1
• ATP-Binding Cassette Transporters (genetics)
• Amyloid beta-Peptides (metabolism, pharmacology)
• Animals
• Apolipoprotein A-I (metabolism)
• Biological Transport, Active (genetics)
• Blood-Brain Barrier (drug effects, metabolism)
• Brain (blood supply, metabolism)
• Cell Line
• Cerebral Arteries (metabolism)
• Endothelial Cells (drug effects, metabolism)
• Humans
• Mice
• Mice, Knockout
• Microinjections
• Peptide Fragments (metabolism, pharmacology)